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Cell. 2002 Jan 25;108(2):247-59.

Autoinhibition of c-Abl.

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1
Developmental Biology Programme, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.

Abstract

Despite years of investigation, the molecular mechanism responsible for regulation of the c-Abl tyrosine kinase has remained elusive. We now report inhibition of the catalytic activity of purified c-Abl in vitro, demonstrating that regulation is an intrinsic property of the molecule. We show that the interaction of the N-terminal 80 residues with the rest of the protein mediates autoregulation. This N-terminal "cap" is required to achieve and maintain inhibition, and its loss turns c-Abl into an oncogenic protein and contributes to deregulation of BCR-Abl.

PMID:
11832214
[Indexed for MEDLINE]
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